Prostate cancer is a common malignant tumor in the western world. In Sweden it ranks as the number one cause of death in malignant disease. No cure exists for advanced or metastasizing cases.
Standard treatment for prostate cancer involves surgical or pharmacological castration, i.e., androgen ablation, leading to remission in 70% of cases. Androgen ablation therapies typically used in the treatment of prostate cancer are designed to inhibit androgen receptor function, since the tumor is usually androgen-dependent. However, most cases relapse and become androgen-refractory disease within about 3 years. Life span is usually less than 1 year after hormone refractory relapse.
Immuno-therapy of prostate cancer by means of single cytokines has so far shown limited results. The response rate of patients to interferon-α is around 5% in hormone-refractory prostate cancer. The response to systemic IL-2 administration is difficult to distinguish from a no treatment control group.
The most promising results so far have been obtained by administration of TNF-α. However, systemic treatment with TNF-α results in side effects that significantly limit the clinical utility of TNF-α.
Δ5-Androstenediol (AED) is a naturally-occurring metabolite of dehydroepiandrosterone (DHEA), the most abundant product of the adrenal glands. AED may also arise from the metabolism of other steroids. AED exists in two epimeric forms: Δ5-androstene-3-β, 17α-diol (αAED) and Δ5-androstene-3-β, 17β-diol (βAED). Both are naturally occurring metabolites of dehydroepiandrosterone (DHEA). βAED has immunostimulating properties and immune upregulating properties. αAED has been shown to induce apoptosis in transformed cells in vitro. Apoptosis, or “programmed cell death,” may be defined as a genetically determined destruction of cells from within due to activation of a stimulus or removal of a suppressing agent or stimulus.
In recent years there has been an increasing interest in the immunological effects of DHEA and other steroids. This has led to experiments where it has been shown that both DHEA in itself, and even more so βAED, protect against otherwise lethal infections. As this effect is not restricted to any single species of pathogenic microorganism, but encompasses RNA and DNA-type viruses, gram-positive and gram-negative bacteria, and parasites, it cannot be explained as an antibiotic effect.
Evaluation of the immune regulating effect of steroids has been accomplished using the methods first disclosed in U.S. Pat. No. 5,387,583, which is incorporated herein by reference.
Studies have shown that βAED treatment of lymphocytes previously stimulated with concanavalin A (con A), leads to increasing amounts of IL2, IL3 and TNF-α. Adding cortisone to a lymphocyte culture stimulated with con A leads to diminished quantities of cytokines IL-2 and IL-3. The effect of cortisone can be counteracted by adding βAED.